Telomerase function genetic instability cell proliferation and cancer metastasis

Cellular transformation leading to the immortalisation of cells and to apoptotic death of cells is associated with characteristic chromosomal abnormalities. The chromosomal entities that are involved in the generation of these abnormalities have been identified in the past few years and there has been a significant advance in our understanding of the molecular mechanisms involved in the immortalisation of cells and limitation of the life span of cells by apoptotic processes. This area of study...

The role ofselectins in cancer dissemination

The cellular adhesion molecules, called the selectins, bind to carbohydrate antigens present on endothelial cells activated by cytokines. E-selectin, for example, has been shown to bind to the carbohydrate antigens sialyl Lewis (x) and sialyl Lewis (a) (Lowe et al., 1990 Phillips et al., 1990 Walz et al., 1990 Takada et al., 1991 Tiemeyer et al., 1991). The selectins are known to be expressed in human tumours and this could enhance tumour cell adhesion to endothelial cells. Tumour cells may...

The regulatory role of p53 in GrS and G2M transition in cell cycle progression

The progression of the cell cycle is monitored for DNA damage at the GrS and G2-M boundaries and cells with DNA damage are detained at either of these checkpoints pending appropriate DNA repair. Lane (1992) proposed the renowned 'guardian of the genome' role for p53, regulating the entry of cells into the S-phase following DNA repair and failing this the cells enter the apoptotic pathway. At the G,-S checkpoint any damage sustained by cellular DNA is repaired with great fidelity. A normal...

Cell proliferation in Wilms tumour

The cellular components of Wilms' tumour show marked differences in proliferative activity. Delahunt et al. (1994) assessed this by measuring the expression of proliferating cell nuclear antigen (PCNA) and silver-staining nucleolar organiser region (AgNOR). They found that the blastemal and epithelial components showed far greater proliferative ability than the stromal component and there was also an indication that the proliferative activity, as determined by these methods, might be related to...

Cyclindependent kinase cdk inhibitors as tumour suppressors

In recent years, a number of genes which encode proteins capable of functioning as inhibitors of cyclin-dependent kinases have been identified and cloned. Cyclin-dependent kinases (cdks) regulate cell cycle progression. The cdks phosphorylate the rb protein which then allows the progression of cells from Gi into the S-phase. The cdks are activated by phosphorylation by cdk-activating kinases (CAK). The cdk inhibitors block this activation of cdks by CAK. The inhibition of cdk activation results...

HSPs in cancer and their possible relevance to prognosis

Heat shock proteins have been reported to exert a marked suppressive effect on cellular transformation. The suppressive effect could be a consequence of the formation of complexes between HSP and the transforming agents. For instance, transfection of HSP70 into cells transformed by mutant p53 and ras myc oncogenes suppresses the process of transformation (Yehiely and Oren, 1992). Complex formation between p53 and HSPs has also been shown to occur in several human tumours. Davidoff et al. (1992)...

Interaction of p53 with HSPs

The phosphoprotein p53, as we have discussed previously, is able to regulate the GrS transition in the cell cycle. It would appear that p53 is involved, together with HSPs, in a regulatory loop with several genes whose expression is required for cell proliferation. Thus, p53 protein down-regulates the activity of the promoters of several genes, prominent among these are promoters of cfos and c-fun, the immediate early response genes, and also the kctin gene and the HSP70 gene (Ginsberg et al.,...

Neural cell adhesion molecule NCAM in differentiation and cancer

The neural adhesion molecule NCAM and yV-cadherin have been studied intensively for their role in neurite regeneration and neuronal adhesion to other cells. NCAM-mediated cell interactions do not require Ca2+, whereas JV-cadherin is a Ca2+-dependent adhesive protein (see page 103). NCAM, like other CAMs discussed above, also possesses immunoglobulin-like domains (Cunningham et al., 1987). Transfection of cDNAs coding for NCAM into cells which do not express these molecules enhances their...

Regulation of mdm2 by p53

The mdm2 (murine double minute 2) was isolated from transformed mouse 3T3 cells and its expression was associated with high tumorigenic potential (Cahilly-Snyder et al, 1987 Fakharzadeh et al., 1991). This gene has been mapped to chromosome 12ql3. The mdm2 gene is amplified in a number of human malignancies. Multiple transcripts of mdm2 have been detected in breast epithelial cells, with protein products ranging from 54-68 kDa to 90-100 kDa (Gudas et al, 1995a). mdm2 has been shown to bind p53...